There is sufficient evidence indicating that glucocorticoids, thyroid hormone, and insulin are involved in the regulation of fetal lung maturation. The understanding of their precise role in lung growth, cell differentiation and surfactant production and of the factors which modify cell sensitivity to each of these hormones is the major objective of these studies. A primary culture system of fetal lung cell populations highly enriched in type II cells, recently developed in our laboratory, will be further characterized and used to define the role of each hormone in cell growth and differentiation (appearance of lamellar bodies), phospholipid and protein metabolism, and the activity of enzymes involved in lecithin synthesis. The synergistic and antagonistic effects (e.g. cortisol-insulin antagonism) of hormones in these processes will be studied and the possible mechanisms involved will be investigated by measuring receptor levels and their hormonal regulation in vivo and in cell culture. The binding of insulin to both cell surface and intracellular receptor sites as well as the regulation of these sites will be investigated and correlated with the effects of insulin on cell growth and differentiation. Binding of agonists in the absence or presence of antagonists and biological response will be correlated to assess the physiological significance of the binding proteins (receptors). Since the effects of glucocorticoids, and possibly of thyroxine and insulin, on lung maturation are age-dependent, some of the factors determining hormone cell responsiveness will be investigated by examining the ontogenic development of receptors, and by comparing the properties of glucocorticoid receptors and their nuclear acceptor sites, the patterns of chromosomal proteins, and the effects of glucocorticoids on the synthesis or modification (acetylation, phosphorylation) of histones and nonhistones, in lungs from early and late gestation fetuses. The role of glucocorticoids in the development of glucagon receptors will be examined as a possible mechanism for the age-related action of glucocorticoids in glucagen metabolism.